We propose to use electrospinning to fabricate a dermal equivalent composed of nano and micron scale diameter fibrils of collagen and elastin. Electrospinning is a rapid, and efficient, nanotechnology that uses an electric field to process synthetic and natural protein polymers into tissue-engineering scaffolds Tissue-engineering scaffolds composed of electrospun collagen are resilient, non-immunogenic and fully bioresorbable. When implanted as a dermal equivalent, this material is rapidly infiltrated by dermal fibroblasts, microvascular endothelial cells and epithelial cells. We attribute the """"""""stealthy nature"""""""" and biological activity of electrospun collagen to the chemical composition of the polymer, the near physiological diameter of the fibers (100-200nm) and the 67 nm repeat feature that is observed at the ultrastructural level on these filaments. This 67 nm repeat is present on native collagen and is associated with specific binding sites that promote the migration of dermal and endothelial cells. From a commercial and clinical prospective, scaffolds of electrospun collagen have several distinct advantages: this material can be stored in a dry, sterile state to increase shelf-life, are easy to deploy and highly hemostatic. In addition, electrospun scaffolds can be supplemented with anti-bacterial agents, other pharmaceuticals like topical anesthetics and peptide growth factors during the fabrication process, providing enormous flexibility in the design of a tissue engineering scaffold.
The Specific Aims of this Project are:
Aim 1. Tailor an electrospinning device for the fabrication of a dermal equivalent composed of nano-scale to micron-scale diameter fibrils of native ECM constituents.
Aim 2. Evaluate the mechanical and biological properties of a dermal equivalent as a function of composition and fiber diameter.
Aim 3. Use the structure of a nanofabricated dermal equivalent as a novel solid-phase delivery platform for anti-bacterial agents.
Aim 4. Evaluate candidate dermal equivalents in a full thickness dermal injury in the guinea pig.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003087-02
Application #
6882042
Study Section
Special Emphasis Panel (ZRG1-BBCB (50))
Program Officer
Moy, Peter
Project Start
2004-04-15
Project End
2008-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
2
Fiscal Year
2005
Total Cost
$300,150
Indirect Cost
Name
Virginia Commonwealth University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Newton, Dan; Mahajan, Raul; Ayres, Chantal et al. (2009) Regulation of material properties in electrospun scaffolds: Role of cross-linking and fiber tertiary structure. Acta Biomater 5:518-29
Ayres, Chantal E; Jha, B Shekhar; Meredith, Hannah et al. (2008) Measuring fiber alignment in electrospun scaffolds: a user's guide to the 2D fast Fourier transform approach. J Biomater Sci Polym Ed 19:603-21
Ayres, Chantal E; Bowlin, Gary L; Pizinger, Ryan et al. (2007) Incremental changes in anisotropy induce incremental changes in the material properties of electrospun scaffolds. Acta Biomater 3:651-61
Simpson, David G (2006) Dermal templates and the wound-healing paradigm: the promise of tissue regeneration. Expert Rev Med Devices 3:471-84
Ayres, Chantal; Bowlin, Gary L; Henderson, Scott C et al. (2006) Modulation of anisotropy in electrospun tissue-engineering scaffolds: Analysis of fiber alignment by the fast Fourier transform. Biomaterials 27:5524-34
Telemeco, T A; Ayres, C; Bowlin, G L et al. (2005) Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning. Acta Biomater 1:377-85